Interaction between fibrinogen and IL-6 genetic variants and associations with cardiovascular disease risk in the Cardiovascular Health Study.
Interaction between fibrinogen and IL-6 genetic variants and associations with cardiovascular disease risk in the Cardiovascular Health Study.
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DOI：
10.1111/j.1469-1809.2009.00551.x
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发表时间：
2010-01
影响因子：
1.9
通讯作者：
Reiner AP
中科院分区：
文献类型：
--
作者：
Carty CL;Heagerty P;Heckbert SR;Jarvik GP;Lange LA;Cushman M;Tracy RP;Reiner AP
炎性细胞因子白细胞介素-6（IL-6）是纤维蛋白原合成的主要调节因子，尽管其与纤维蛋白原基因（FGA、FGB、FGG）的相互作用与CVD风险的关系在人类中尚未得到充分研究。我们在3900名参加心血管健康研究的欧美人中调查了常见纤维蛋白原和IL 6 tagSNPs与纤维蛋白原水平、颈动脉内膜中层厚度（IMT）和心肌梗死（MI）或缺血性卒中风险的联合相关性。为了确定与每个结果相关的遗传主效应和相互作用的组合，我们使用了逻辑回归。我们还评估了纤维蛋白原SNPs和纤维蛋白原水平之间的关系是否因IL-6水平而异，使用线性回归模型与乘法相互作用项。纤维蛋白原和IL 6 SNP的组合与纤维蛋白原水平相关（p<0.005），但与IMT（p>0.30）、MI（p=0.73）或中风（p=0.21）无关。在具有FGB 1437（rs 1800790）次要等位基因和缺乏FGA 6534（rs6050）次要等位基因的个体中，纤维蛋白原水平较高;这些SNP与IL 6 rs 1800796相互作用以影响纤维蛋白原水平。检测到IL-6水平与位于与纤维蛋白原水平相关的FGA和FGG启动子区域的SNP之间存在边缘显着（p=0.03）的相互作用。我们确定了影响纤维蛋白原水平的潜在基因-基因相互作用。虽然IL-6反应性结合位点存在于纤维蛋白原基因启动子区域，但我们没有发现纤维蛋白原SNP和IL-6 SNP之间相互作用或影响CVD风险的水平的有力证据。
The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) in relation to CVD risk is not well-studied in humans. We investigated joint associations of common fibrinogen and IL6 tagSNPs with fibrinogen level, carotid intima-media thickness (IMT) and risk of myocardial infarction (MI) or ischemic stroke in 3900 European-American participants of the Cardiovascular Health Study. To identify combinations of genetic main effects and interactions associated with each outcome, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen and IL6 SNPs were associated with fibrinogen level (p<0.005), but not with IMT (p>0.30), MI (p=0.73) or stroke (p=0.21). Fibrinogen levels were higher in higher in individuals having FGB1437 (rs1800790) minor alleles and lacking FGA6534 (rs6050) minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen level. Marginally significant (p=0.03) interactions between IL-6 level and SNPs located in promoter regions of FGA and FGG associated with fibrinogen levels were detected. We identified potential gene-gene interactions influencing fibrinogen levels. Although IL-6 responsive binding sites are present in fibrinogen gene promoter regions, we did not find strong evidence of interaction between fibrinogen SNPs and IL6 SNPs or levels influencing CVD risk.
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影响因子：
2.1
作者：
Kooperberg, C;Ruczinski, I;Hsu, L
通讯作者：
Hsu, L
DOI：
10.1161/01.atv.0000040224.49362.60
发表时间：
2002-12-01
影响因子：
8.7
作者：
Jenny, NS;Tracy, RP;Humphries, SE
通讯作者：
Humphries, SE
DOI：
10.1161/01.atv.0000143856.01669.e7
发表时间：
2004-11-01
影响因子：
8.7
作者：
de Maat, MPM;Bladbjerg, EM;Christensen, K
通讯作者：
Christensen, K
影响因子：
15.9
作者：
Fishman, D;Faulds, G;Woo, P
通讯作者：
Woo, P
影响因子：
1.9
作者：
Kannel, WB
通讯作者：
Kannel, WB